tbuckley/cabot-search huggingface dataset:
A lentiviral vector for the production of T cells with an inducible transgene and a constitutively expressed tumour-targeting receptor
Authors: Patrick Reichenbach, Greta Maria Paola Giordano Attianese, Khaoula Ouchen, Elisabetta Cribioli, Melanie Triboulet, Sarah Ash, Margaux Saillard, Romain Vuillefroy de Silly, George Coukos, Melita Irving
Journal: Nature Biomedical Engineering (2023)

Abstract Vectors that facilitate the engineering of T cells that can better harness endogenous immunity and overcome suppressive barriers in the tumour microenvironment would help improve the safety and efficacy of T-cell therapies for more patients. Here we report the design, production and applicability, in T-cell engineering, of a lentiviral vector leveraging an antisense configuration and comprising a promoter driving the constitutive expression of a tumour-directed receptor and a second promoter enabling the efficient activation-inducible expression of a genetic payload. The vector allows for the delivery of a variety of genes to human T cells, as we show for interleukin-2 and a microRNA-based short hairpin RNA for the knockdown of the gene coding for haematopoietic progenitor kinase 1, a negative regulator of T-cell-receptor signalling. We also show that a gene encoded under an activation-inducible promoter is specifically expressed by tumour-redirected T cells on encountering a target antigen in the tumour microenvironment. The single two-gene-encoding vector can be produced at high titres under an optimized protocol adaptable to good manufacturing practices.
We must not turn away from crimes against humanity in Iran
Authors: Katrin Rabiei
Journal: BMJ (2023)

Over the past 44 years, the regime in Iran has indiscriminately jailed, tortured, abused, and murdered dissidents, religious minorities, LGBT+ people, and high profile figures who have spoken out against the regime, such as artists, academics, authors, athletes, and journalists. 1 -4 Acts of resistance-however minor-such as choosing your own faith or any perceived act of defiance against the regime have been met with the harshest penalties. 1 -3 5 Often that means death.
Thymidine kinase 1 drives hepatocellular carcinoma in enzyme-dependent and -independent manners
Authors: Qing Li, Liren Zhang, Qin Yang, Mei Li, Xiongxiong Pan, Jiali Xu, Chen Zhong, Feifan Yao, Ruizhi Zhang, Suiqing Zhou, Xinzheng Dai, Xiaoli Shi, Yongjiu Dai, Jing Xu, Xu Cheng, Wenchang Xiao, Zhigang She, Ke Wang, Xiaofeng Qian, Liyong Pu, Peng Zhang, Xuehao Wang
Journal: Cell Metabolism (2023)
Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex
Authors: Aleksandra Mezydlo, Nils Treiber, Emily Melisa Ullrich Gavilanes, Katharina Eichenseer, Mihai Ancău, Adinda Wens, Carla Ares Carral, Martina Schifferer, Nicolas Snaidero, Thomas Misgeld, Martin Kerschensteiner
Journal: Neuron (2023)
The global fatty liver disease Sustainable Development Goal country score for 195 countries and territories
Authors: Jeffrey V. Lazarus, Hannah Han, Henry E. Mark, Saleh A. Alqahtani, Jörn M. Schattenberg, Joan B. Soriano, Trenton M. White, Shira Zelber-Sagi, M. Ashworth Dirac
Journal: Hepatology (2023)

Background and Aims: Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens. Approach and Results: We developed 2 fatty liver disease–SDG score sets. The first included 6 indicators (child wasting, child overweight, noncommunicable disease mortality, a universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries and territories between 1990 and 2017. The second included the aforementioned indicators plus an urban green space indicator, covering 60 countries and territories for which 2017 data were available. To develop the fatty liver disease–SDG score, indicators were categorized as “positive” or “negative” and scaled from 0 to 100. Higher scores indicate better preparedness levels. Fatty liver disease–SDG scores varied between countries and territories (n = 195), from 14.6 (95% uncertainty interval: 8.9 to 19.4) in Niger to 93.5 (91.6 to 95.3) in Japan; 18 countries and territories scored &gt; 85. Regionally, the high-income super-region had the highest score at 88.8 (87.3 to 90.1) in 2017, whereas south Asia had the lowest score at 44.1 (42.4 to 45.8). Between 1990 and 2017, the fatty liver disease–SDG score increased in all super-regions, with the greatest increase in south Asia, but decreased in 8 countries and territories. Conclusions: The fatty liver disease–SDG score provides a strategic advocacy tool at the national and global levels for the liver health field and noncommunicable disease advocates, highlighting the multisectoral collaborations needed to address fatty liver disease, and noncommunicable diseases overall.
Metabolic independence drives gut microbial colonization and resilience in health and disease
Authors: Andrea R. Watson, Jessika Füssel, Iva Veseli, Johanna Zaal DeLongchamp, Marisela Silva, Florian Trigodet, Karen Lolans, Alon Shaiber, Emily Fogarty, Joseph M. Runde, Christopher Quince, Michael K. Yu, Arda Söylev, Hilary G. Morrison, Sonny T. M. Lee, Dina Kao, David T. Rubin, Bana Jabri, Thomas Louie, A. Murat Eren
Journal: Genome biology (2023)

Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.
Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial
Authors: Delphine Réa, Carla Boquimpani, Michael J. Mauro, Yosuke Minami, Alex Allepuz, Vikalp Kumar Maheshwari, Denise D’Alessio, Ying Wu, Rachael Lawrance, Sarunas Narbutas, Giora Sharf, Andreas Hochhaus
Journal: Leukemia (2023)

In ASCEMBL, an open-label, randomized Phase 3 study, asciminib demonstrated superior efficacy and better safety profile compared with bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors. Health-related quality of life (HRQOL) reported by patients is key to understanding the benefit and impact of treatment on patients' lives, and is becoming increasingly important as the life expectancy of CML-CP patients increases and patients require long-term treatment. In ASCEMBL, patients completed questionnaires to assess CML symptoms and interference with daily life (M.D. Anderson Symptom Inventory - CML [MDASI-CML]), general HRQOL (five-level EQ-5D [EQ-5D-5L], Patient Global Impression of Change - CML [PGIC-CML]), and impact of CML on working life and activity (Work Productivity and Activity Impairment questionnaire - CML [WPAI-CML]). Patients' CML symptoms and HRQOL remained stable during 48 weeks of treatment with asciminib, with a general trend for decreased CML symptom severity, particularly for fatigue, and improvement in HRQOL. A clinically meaningful increase in diarrhea severity was observed in patients treated with bosutinib compared to asciminib. These data provide better understanding of the patient perspective and treatment impact on HRQOL in a later-line setting, where little information has been published to date.
Granulocyte Colony-Stimulating Factor in Severe Chemotherapy-Induced Afebrile Neutropenia
Authors: Lynn C. Hartmann, Loren K. Tschetter, Thomas M. Habermann, Larry P. Ebbert, P. Steven Johnson, James A. Mailliard, Ralph Levitt, Vera J. Suman, Thomas E. Witzig, H.S. Wieand, Langdon L. Miller, Charles G. Moertel, Darryl C. Grendahl, Dianne M. Herrera
Journal: New England Journal of Medicine (1997)

Randomized trials of colony-stimulating factors in febrile patients with neutropenia after chemotherapy have not consistently shown clinical benefit. Nevertheless, the use of colony-stimulating factors to treat patients with chemotherapy-induced neutropenia is widespread.
Effectiveness and safety of (adeno) tonsillectomy for pediatric obstructive sleep apnea in different age groups: A systematic review and meta-analysis
Authors: Yijing Chen, Jinkun Xu, Guoping Yin, Jingying Ye
Journal: Sleep Medicine Reviews (2023)

This meta-analysis aimed to assess the effectiveness and safety of (adeno)tonsillectomy (AT) for uncomplicated pediatric obstructive sleep apnea (OSA) across different age groups. Four electronic databases were searched until April 2022, and 93 studies (9087 participants) were selected, including before-after studies, cohort studies, and randomized controlled trials. It has been suggested that age, disease severity, and length of follow-up are associated with surgical effects. Compared with older children (>7 years), patients receiving AT surgery before the age of 7 exhibited a significantly greater release of disease severity, as well as a greater decrease in hypoxemic burden, improvement in sleep quality, and better cardiovascular function. Cognitive/behavioral performance also improved after AT, although it was more related to the length of follow-up than the age at surgery. Notably, the surgical complication rate was considerably higher in patients younger than 3 years old. Overall, we suggest that the age of 3–7 years might be optimal for AT in polysomnography-diagnosed uncomplicated OSA to maximize potential benefits for both disease and comorbidities and balance the risks of surgery.
Phototriggered structures: Latest advances in biomedical applications
Authors: Mojtaba Shamsipur, Atefeh Ghavidast, Afshin Pashabadi
Journal: Acta Pharmaceutica Sinica B (2023)

Non-invasive control of the drug molecules accessibility is a key issue in improving diagnostic and therapeutic procedures. Some studies have explored the spatiotemporal control by light as a peripheral stimulus. Phototriggered drug delivery systems (PTDDSs) have received interest in the past decade among biological researchers due to their capability the control drug release. To this end, a wide range of phototrigger molecular structures participated in the DDSs to serve additional efficiency and a high-conversion release of active fragments under light irradiation. Up to now, several categories of PTDDSs have been extended to upgrade the performance of controlled delivery of therapeutic agents based on well-known phototrigger molecular structures like o-nitrobenzyl, coumarinyl, anthracenyl, quinolinyl, o-hydroxycinnamate and hydroxyphenacyl, where either of one endows an exclusive feature and distinct mechanistic approach. This review conveys the design, photochemical properties and essential mechanism of the most important phototriggered structures for the release of single and dual (similar or different) active molecules that have the ability to quickly reason of the large variety of dynamic biological phenomena for biomedical applications like photo-regulated drug release, synergistic outcomes, real-time monitoring, and biocompatibility potential.
Optimized CAR-T therapy based on spatiotemporal changes and chemotactic mechanisms of MDSCs induced by hypofractionated radiotherapy
Authors: Benxia Zhang, Min Hu, Qizhi Ma, Kai Li, Xue Li, Xia He, Pei Shu, Yue Chen, Ge Gao, Diyuan Qin, Fuchun Guo, Jian Zhao, Ning Liu, Kexun Zhou, MingYang Feng, Weiting Liao, Dan Li, Xin Wang, Yongsheng Wang
Journal: Molecular Therapy (2023)

Poor intratumoral infiltration is the major challenge for chimeric antigen receptor (CAR)-T cell therapy in solid tumors. Hypofractionated radiotherapy (HFRT) has been reported to induce immune cell infiltration and reshape the tumor immune microenvironment. Here, we showed that HFRT (5 × 5 Gy) mediated an early accumulation of intratumoral myeloid-derived suppressor cells (MDSCs) and decreased infiltration of T cells in the tumor microenvironment (TME) of immunocompetent mice bearing triple-negative breast cancer (TNBC) or colon cancer, which was further confirmed in tumors from patients. RNA sequencing (RNA-seq) and cytokine profiling analysis revealed that HFRT induced the activation and proliferation of tumor-infiltrated MDSCs, which was mediated by the interactions of multiple chemokines and chemokine receptors. Further investigation showed that when combined with HFRT, CXCR2 blockade significantly inhibited MDSCs trafficking to tumors and effectively enhanced the intratumoral infiltration and treatment efficacy of CAR-T cells. Our study demonstrates that MDSCs blockade combined with HFRT is promising for CAR-T cell therapy optimization in solid tumors.Graphical abstract
Focussed Assessment with Sonography in acute Lassa Fever (FASLa): Development of a point-of-care protocol and description of common ultrasound findings
Authors: Cyril O Erameh, Till Koch, Osahogie Isaac Edeawe, Lisa Oestereich, Till Omansen, Johannes Jochum, Donatus I Adomeh, Odia Ikponmwonsa, Chris Aire, Meike Pahlmann, Danny A Asogun, Ephraim Ogbaini-Emovon, Sylvanus A Okogbenin, Stephan Günther, Michael Ramharter, Peter E Akideno, Benno Kreuels
Journal: Journal of Infection (2023)
Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA
Authors: Wenxin Zhang, Xiaohui Pan, Yanjun Xu, Hongjie Guo, Mingming Zheng, Xi Chen, Honghai Wu, Fengming Luan, Qiaojun He, Ling Ding, Bo Yang
Journal: Acta Pharmaceutica Sinica B (2023)

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.
Online calculators for predicting the risk of anastomotic stricture after hepaticojejunostomy for bile duct injury after cholecystectomy: a multicenter retrospective study
Authors: Jiangming Chen, Zixiang Chen, Xiyang Yan, Xiaoliang Liu, Debao Fang, Xiang Miao, Zhong Tong, Xiaoming Wang, Zheng Lu, Hui Hou, Cheng Wang, Xiaoping Geng, Fubao Liu
Journal: International Journal of Surgery (2023)

Anastomotic stricture is a common underlying cause of long-term morbidity after hepaticojejunostomy (HJ) for bile duct injury (BDI) following cholecystectomy. However, there are no methods for predicting stricture risk. This study was aimed at establishing two online calculators for predicting anastomotic stricture occurrence (ASO) and stricture-free survival (SFS) in this patient population.The clinicopathological characteristics and follow-up information of patients who underwent HJ for BDI after cholecystectomy from a multi-institutional database were reviewed. Univariate and multivariate analyses of the risk factors of ASO and SFS were performed in the training cohort. Two nomogram-based online calculators were developed and validated by internal bootstrapping resamples ( n =1000) and an external cohort.Among 220 screened patients, 41 (18.64%) experienced anastomotic strictures after a median follow-up of 110.7 months. Using multivariate analysis, four variables, including previous repair, sepsis, HJ phase, and bile duct fistula, were identified as independent risk factors associated with both ASO and SFS. Two nomogram models and their corresponding online calculators were subsequently developed. In the training cohort, the novel calculators achieved concordance indices ( C -indices) of 0.841 and 0.763 in predicting ASO and SFS, respectively, much higher than those of the above variables. The predictive accuracy of the resulting models was also good in the internal ( C -indices: 0.867 and 0.821) and external ( C -indices: 0.852 and 0.823) validation cohorts.The two easy-to-use online calculators demonstrated optimal predictive performance for identifying patients at high risk for ASO and with dismal SFS. The estimation of individual risks will help guide decision-making and long-term personalized surveillance.
Trocar number and placement for laparoscopic sleeve gastrectomy and comparison of single-incision and conventional laparoscopic sleeve gastrectomy: a systematic review and meta-analysis
Authors: Zhengchen Jiang, Zhao Zhang, Tianyi Feng, Yugang Cheng, Guangyong Zhang, Mingwei Zhong, Sanyuan Hu
Journal: International Journal of Surgery (2023)

Background: Conventional laparoscopic sleeve gastrectomy (CLSG) has been conducted in multiple centers for treating morbid obesity, however, there are no standard criteria for (1) placing the trocar; and (2) how many trocars should be used. Single-incision laparoscopic sleeve gastrectomy (SLSG), a newly emerged technique in 2008, has been proposed as an alternative to CLSG in recent years, however, there is no definite evidence for this. Materials and methods: A systematic literature search was performed using the PubMed, Embase, Web of Science, and Cochrane Library databases for laparoscopic sleeve gastrectomy cases from January 2006 to October 2022. We then summarized the trocar numbers and placement patterns among these studies. A meta-analysis was conducted to compare the difference between SLSG and CLSG in the perioperative and postoperative indices. Results: A total of 61 studies involving 20 180 patients who underwent laparoscopic sleeve gastrectomy for treating morbid obesity were included in the systematic review, including 11 on SLSG, 35 on CLSG, and 15 studies comparing SLSG and CLSG. A systematic review showed that the trocar number varied in different CLSG studies, mainly using four or five trocars. The trocars were mainly placed in position, presenting an inverted trapezoid pattern and a left-predominant pattern. Meta-analysis showed that the operative time in the SLSG was significantly higher than that in the CLSG, and the pain Visual Analog Scale rating on postoperative day 1 in the CLSG was significantly higher than in the SLSG. There were no statistical significances in the other complications or surgical efficiency. Conclusions: In the CLSG, the majority of the trocars were arranged in an inverted trapezoid pattern and were of the left-predominant type. Although SLSG is a feasible technique in selected patients, there is insufficient evidence to recommend its widespread use compared with CLSG. High-quality randomized controlled trials with large study populations and long follow-up periods will be required in the future.
Analytical Techniques for Single-Cell Biochemical Assays of Lipids
Authors: Ming Yao, Manibarathi Vaithiyanathan, Nancy L. Allbritton
Journal: Annual Review of Biomedical Engineering (2023)

Lipids are essential cellular components forming membranes, serving as energy reserves, and acting as chemical messengers. Dysfunction in lipid metabolism and signaling is associated with a wide range of diseases including cancer and autoimmunity. Heterogeneity in cell behavior including lipid signaling is increasingly recognized as a driver of disease and drug resistance. This diversity in cellular responses as well as the roles of lipids in health and disease drive the need to quantify lipids within single cells. Single-cell lipid assays are challenging due to the small size of cells (∼1 pL) and the large numbers of lipid species present at concentrations spanning orders of magnitude. A growing number of methodologies enable assay of large numbers of lipid analytes, perform high-resolution spatial measurements, or permit highly sensitive lipid assays in single cells. Covered in this review are mass spectrometry, Raman imaging, and fluorescence-based assays including microscopy and microseparations.
Thinking Beyond the Device: An Overview of Human- and Equity-Centered Approaches for Health Technology Design
Authors: Natalia M. Rodriguez, Grace Burleson, Jacqueline C. Linnes, Kathleen H. Sienko
Journal: Annual Review of Biomedical Engineering (2023)

A shift in the traditional technocentric view of medical device design to a human-centered one is needed to bridge existing translational gaps and improve health equity. To ensure the successful and equitable adoption of health technology innovations, engineers must think beyond the device and the direct end user and must seek a more holistic understanding of broader stakeholder needs and the intended context of use early in a design process. The objectives of this review article are (a) to provide rationale for the need to incorporate meaningful stakeholder analysis and contextual investigation in health technology development and biomedical engineering pedagogy, (b) to review existing frameworks and human- and equity-centered approaches to stakeholder engagement and contextual investigation for improved adoption of innovative technologies, and (c) to present case studyexamples of medical device design that apply these approaches to bridge the gaps between biomedical engineers and the contexts for which they are designing.
Neurotechnology for Pain
Authors: Lee E. Fisher, Scott F. Lempka
Journal: Annual Review of Biomedical Engineering (2023)

Neurotechnologies for treating pain rely on electrical stimulation of the central or peripheral nervous system to disrupt or block pain signaling and have been commercialized to treat a variety of pain conditions. While their adoption is accelerating, neurotechnologies are still frequently viewed as a last resort, after many other treatment options have been explored. We review the pain conditions commonly treated with electrical stimulation, as well as the specific neurotechnologies used for treating those conditions. We identify barriers to adoption, including a limited understanding of mechanisms of action, inconsistent efficacy across patients, and challenges related to selectivity of stimulation and off-target side effects. We describe design improvements that have recently been implemented, as well as some cutting-edge technologies that may address the limitations of existing neurotechnologies. Addressing these challenges will accelerate adoption and change neurotechnologies from last-line to first-line treatments for people living with chronic pain.